The present renewal application consists of three separate projects, based on one simple theme, i.e., the use of in vitro systems to explore radically new ways to improve the performance of chemotherapeutic agents by manipulating target cells or the cells of the host, with particular emphasis on cancer of the colon. The first project deals with the inhibitory effect of normal cells on the growth of neoplastic cells. It is based on the development of a co-culture system in which normal and neoplastic cells are grown together. The second project deals with mutagenesis and is based on preliminary results of Warren Nichols and co-workers in Camden, N.J. The third project is based on the well-established finding that cells in the early S phase of the cell cycle are more easily killed by certain drugs acting on the DNA synthetic mechanism than cells in late S or in any other phase of the cell cycle.